AKI603|cas:1432515-73-5|西域试剂

AKI603,98.05%

产品编号：Bellancom-123159| CAS NO：1432515-73-5| 分子式：C₁₉H₂₃N₉O₂| 分子量：409.45

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货号	价格	库存与货期
Bellancom-123159	￥3500.00	杭州北京（现货）
Bellancom-123159	￥5800.00	杭州北京（现货）
Bellancom-123159	￥11000.00	杭州北京（现货）

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AKI603

产品介绍

AKI603 是一种极光激酶 A (AurA) 抑制剂，其 IC₅₀ 值为 12.3 nM，被开发用于克服白血病中 BCR-ABL-T315I 耐药性突变。AKI603 对白血病细胞具有很强的抗增殖活性。

生物活性

AKI603 is an inhibitor of Aurora kinase A (AurA), with an IC₅₀ of 12.3 nM. AKI603 is developed to overcome resistance mediated by BCR-ABL-T315I mutation. AKI603 exhibits strong anti-proliferative activity in leukemic cells.

体外研究

AKI603 (0.039-0.6 μM; 48 hours) extensively inhibits proliferation of leukemia cells.
AKI603 (0.039-0.6 μM; 48 hours) significantly inhibits the phosphorylation of AurA in NB4, K562, and Jurkat cell lines in a dose-dependent manner while the level of total AurA protein is not changed.
AKI603 inhibits the proliferation and colony formation of imatinib resistant CML cells.
AKI603 (0.3-0.6 μM; 48 hours) inhibits cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation.
Inhibition of AurA by AKI603 induces leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells.
AKI603 exhibits inhibitory activities on breast cancer cell proliferation, such as SUM149 (IC₅₀=2.04), BT549 (IC₅₀=0.86), MCF-7 (IC₅₀=0.97), MCF-7-Epi (IC₅₀=21.01), Sk-br-3 (IC₅₀=0.73), MDA-MB-231 (IC₅₀=3.49), MDA-MB-453 (MTT, IC₅₀=0.18; Cell counting, IC₅₀=0.19), MDA-MB-468 (MTT, IC₅₀=0.15; Cell counting, IC₅₀=0.17).

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay

Cell Line:	U937 cells, HL-60 cells, NB4 cells, KBM5 cells, K562 cells, Jurkat cells
Concentration:	0.039 μM, 0.078 μM, 0.16 μM, 0.3 μM, 0.6 μM
Incubation Time:	48 hours
Result:	Inhibited all the tested cell lines.

Western Blot Analysis

Cell Line:	NB4 cells, K562 cells, Jurkat cells
Concentration:	0.039 μM, 0.078 μM, 0.16 μM, 0.3 μM, 0.6 μM
Incubation Time:	48 hours
Result:	Inhibited the phosphorylation of AurA Thr288 (p-AurA).

Cell Cycle Analysis

Cell Line:	K562, K562/G, 32D-p210 and 32D-T315I cells
Concentration:	0.3 μM, 0.6 μM
Incubation Time:	48 hours
Result:	Induced polyploidization in the tested cells.

体内研究
(In Vivo)

AKI603 (12.5-25 mg/kg; i.p.; every 2 days; for 14 days) abrogates the growth of xenografted KBM5-T315I cells in nude mice.
AKI603 exhibits moderate oral bioavailability (rat 28.7%) and C_max (rat 202.4 μg/L) following oral administration (rat 25 mg/kg).
AKI603 exhibits terminal elimination half-life (rat 8.9 h) following intravenous administration (rat 2.5 mg/kg).

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female BALB/c nude mice, with KBM5-T315I cells xenografted
Dosage:	12.5 mg/kg, 25 mg/kg
Administration:	Intraperitoneal injection, every 2 days, for 14 days
Result:	Significantly inhibited the growth of tumors.

Animal Model:	SD rats (220-280 g)
Dosage:	2.5 mg/kg for i.v.; 25 mg/kg for p.o. (Pharmacokinetic Analysis)
Administration:	Intravenous injection, oral administration
Result:	Oral bioavailability (28.7%), C_max (202.4 μg/L), T_1/2 (8.9 h)

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female BALB/c nude mice, with KBM5-T315I cells xenografted
Dosage:	12.5 mg/kg, 25 mg/kg
Administration:	Intraperitoneal injection, every 2 days, for 14 days
Result:	Significantly inhibited the growth of tumors.

Animal Model:	SD rats (220-280 g)
Dosage:	2.5 mg/kg for i.v.; 25 mg/kg for p.o. (Pharmacokinetic Analysis)
Administration:	Intravenous injection, oral administration
Result:	Oral bioavailability (28.7%), C_max (202.4 μg/L), T_1/2 (8.9 h)

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Female BALB/c nude mice, with KBM5-T315I cells xenografted
Dosage:	12.5 mg/kg, 25 mg/kg
Administration:	Intraperitoneal injection, every 2 days, for 14 days
Result:	Significantly inhibited the growth of tumors.

Animal Model:	SD rats (220-280 g)
Dosage:	2.5 mg/kg for i.v.; 25 mg/kg for p.o. (Pharmacokinetic Analysis)
Administration:	Intravenous injection, oral administration
Result:	Oral bioavailability (28.7%), C_max (202.4 μg/L), T_1/2 (8.9 h)

性状

Solid

溶解性数据

In Vitro:

DMSO : 125 mg/mL (305.29 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.4423 mL	12.2115 mL	24.4230 mL
5 mM	0.4885 mL	2.4423 mL	4.8846 mL
10 mM	0.2442 mL	1.2212 mL	2.4423 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: 6.25 mg/mL (15.26 mM); Suspended solution; Need ultrasonic

此方案可获得 6.25 mg/mL (15.26 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。
以 1 mL 工作液为例，取 100 μL 62.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液